Expression of Lectin-like Oxidized LDL Receptor-1 in Human Atherosclerotic Lesions (original) (raw)
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LOX-1, OxLDL, and Atherosclerosis
Mediators of Inflammation, 2013
Oxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects.
2006
LOX-1, a lectin-like 52-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. This receptor is upregulated by ox-LDL itself and by angiotensin II, endothelin, cytokines, and shear stress, all participants in atherosclerosis. This receptor is upregulated in the arteries of hypertensive, dyslipidemic, and diabetic animals. Upregulation of LOX-1 has been identified in atherosclerotic arteries of several animal species and humans, not only on the endothelial lining, but also in the neovasculature of the atherosclerotic plaque, and this receptor is often co-localized with apoptotic cells. Recent studies show upregulation of LOX-1 in the ischemic-reperfused myocardium. LOX-1 inhibition is associated with attenuation of atherosclerosis and associated ischemic injury. LOX-1 may be a novel, exciting target for drug therapy.
Oxidized-LDL and Atherosclerosis: Role of LOX-1
Annals of the New York Academy of Sciences, 2006
Recently, we identified the novel receptor for oxidized LDL, named LOX-1. We summarize the importance of the interaction between oxidized LDL and its receptor, LOX-1, in terms of early stage atherogenesis.
Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis
Current Atherosclerosis Reports, 2012
Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation. Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis, and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects of LOX-1 blockade.
The LOX1 Scavenger Receptor and Atherosclerotic Plaque Rupture
Atherosclerosis is a chronic systemic inflammatory disease; the end-stage of which is plaque rupture. This depends on plaque composition and vulnerability rather than the severity of stenosis . Vulnerable plaques are associated with an intense inflammatory response and a thin fibrous cap . Remodeling and degradation of the extracellular matrix (ECM) and fibrous cap are maintained by the products of inflammatory cells . The lectin-like oxidized low-density lipoprotein scavenger receptor (LOX-1) is an increasing focus of attention for molecular, cellular, and clinical studies. Recent genetic studies have identified a strong link between several single nucleotide polymorphisms on the LOX-1 gene and the risk of acute coronary syndrome (ACS) . We review how the LOX-1 receptor and its ligand, oxidized low-density lipoprotein (oxLDL), are implicated at critical stages of plaque destabilization and rupture.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2000
A novel lectinlike oxidized low density lipoprotein receptor-1 (LOX-1) was recently identified in bovine aortic endothelial cells. It is strongly suggested to have a potential role in the initiation and development of atherosclerosis. In this study, we have isolated cDNA clones encoding the rabbit homologue of LOX-1 by screening a rabbit placenta cDNA library. In amino acid sequence and domain structure organization, the rabbit LOX-1 is highly conserved with the human counterpart. Transfection of rabbit LOX-1 cDNA to HEK-293 cells confers on them the activity to bind and internalize oxidized low density lipoprotein. Rabbit LOX-1 was identified as a 45-kDa protein by Western blot analysis with a specific monoclonal antibody. Notably, analyses by reverse transcription-polymerase chain reaction and Western blot revealed that LOX-1 was accumulated in 8-week-old Watanabe heritable hyperlipidemic rabbit aortas compared with normal rabbit aortas. Immunostaining confirmed that the augmented expression of LOX-1 was primarily localized within the intima at the earliest stages of atherogenesis. The most prominent staining was in the endothelial cells of lesions. Furthermore, the distinctive staining of LOX-1 was identified in the endothelium of nonlesion areas of Watanabe heritable hyperlipidemic rabbit aortas. Taken together, these findings support the possibility that LOX-1 might be involved in the initiation of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2000;20:1107-1115.) Key Words: atherosclerosis Ⅲ endothelium Ⅲ oxidized low density lipoproteins Ⅲ lectinlike oxidized low density lipoprotein receptor-1 Ⅲ
Atherosclerosis, 2011
Objective: Lectin-like oxidized LDL receptor-1 (LOX-1), the endothelial receptor for OxLDL, is believed to be responsible for a number of OxLDL-induced effects in the endothelium. Methods and results: In the present study we showed that LDL modified by 15-lipoxygenase (15LO-LDL), a form of minimally modified lipoprotein, beside its ability to induce pro-inflammatory responses such as oxidative stress and the expression of adhesion molecules, significantly increases LOX-1 expression in endothelial cells, both at transcriptional and at protein level. Such effect is likely to be mediated by p38 MAPK and NF-kB pathways. We then permanently overexpressed LOX-1 in an endothelial cell line and showed that 15LO-LDL were a ligand for LOX-1, and that the interaction LOX-1/15LO-LDL upregulated ICAM-1 surface expression. Conclusion: Altogether these results indicate minimally modified LDL as a new inducer for LOX-1 expression and as a new ligand for LOX-1.